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Background/purpose: Recent studies have shown that serum vitamin D deficiency is a negative predictor of response to peginterferon plus ribavirin therapy for Caucasian patients with chronic hepatitis C (CHC). Whether vitamin D receptor (VDR) gene polymorphisms associate with antiviral response in Asian CHC patients remains unclear.Methods: We recruited 139 Asian patients with CHC genotype-1 who achieved 80/80/80 adherence of response-guided peginterferon plus ribavirin therapy. BsmI rs1544410, ApaI rs7975232, and TaqI rs731236 were genotyped and related to clinical and virological features and to treatment outcome.Results: Patients carrying bAt [CCA] haplotype (p=0.033), ApaI CC genotype (p = 0.033), and TaqI AA genotype (p = 0.037) had a higher HCV load as compared to those with other haplotypes, ApaI CA/AA genotype and TaqI AG genotype, respectively. A sustained virological response (SVR) was achieved in 74 (53%) of the patients. Polymorphisms in VDR gene did not correlate with rapid virological response and SVR achievement. Stepwise logistic regression analysis showed that rs12979860 CC type [odds ratio (OR): 5.56, p=0.007], platelet counts ≥ 15 × 10(10)/L (OR: 4.80, p=0.001), and rapid virological response achievement (OR: 8.36, p<0.001) were independent factors of SVR.Conclusion: Despite their associations with high hepatitis C virus load, VDR gene polymorphisms are not related to the response to peginterferon plus ribavirin therapy in Asian CHC patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Prospective, long-term reports and predictors of outcome of endoscope-guided pneumatic dilation are lacking in the literature. The aim of this prospective 7-year follow-up study is to report the efficacy of endoscope-guided pneumatic dilation and determine the possible confounding factors related to remission.Methods: Between January 1998 and June 2004, 32 patients were enrolled. Each patient was treated with endoscope-guided pneumatic dilation and followed-up at regular intervals for a median of 4.5 years. Remission was determined with the use of a structured interview and a previously described symptom score. Cumulative remission rate was analyzed by using the Kaplan-Meier method with assessment of symptom scores between grades before and after PD at 6 weeks, 6 months, 1 year, and then every year after. Possible confounding factors related to the remissions were analyzed by Cox's proportional hazard model.Results: Complete follow-up until August 2007 was obtained in 100% of all patients. Cumulative remissions were 1 year (86.7%), 2 years (86.7%), 3 years (80.0%), 4 years (76.5%), 5 years (72.9%), 6 years (61.7%), and 7 years (61.7%), respectively. Age is a relevant confounding factor to the remissions showing a worse outcome for those under 45 (p = 0.046). One esophageal perforation occurred (3.3%).Conclusions: Endoscope-guided PD itself is safe and modestly effective for up to 7 years investigations in current study. Older patients (>45 years) have favorable overall clinical remissions. [ABSTRACT FROM AUTHOR]

Background & Aims Polymorphisms in interferon ( IFN ) L3 (encodes IFNλ3 or interleukin 28B) are associated with outcomes of treatment for hepatitis C virus (HCV) infection. However, there is controversy regarding how polymorphisms in IFNL3 affect the risk for development of hepatocellular carcinoma (HCC) in patients treated with pegylated interferon and ribavirin. Methods In a retrospective study, we analyzed data from 1118 patients with HCV infection (589 men; median age, 60 y; 49.9% infected with genotype 1; 51.3% with advanced fibrosis) treated with pegylated interferon and ribavirin from March 2000 through October 2009 at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan (71.64% achieved sustained virologic response [SVR]). Baseline samples were collected before therapy. Starting 24 weeks after treatment, clinical and biochemical features were assessed every 3 to 6 months and patients underwent ultrasound examinations. Lesions detected were examined by computed tomography, angiography, or fine-needle aspiration biopsy analyses. Patients were followed up from the initiation of HCV therapy until a diagnosis of HCC (based on published guidelines), death, or March 31, 2013 (median, 60 mo). DNA samples from each patient were analyzed for rs12979860 in IFNL3 . Kaplan–Meier analysis was used to determine the risk for development of HCC. Results The percentages of patients with the IFNL3 rs12979860 CC, CT, and TT genotypes were 86.4%, 13.2%, and 0.3%, respectively. A total of 108 patients (9.66%) developed HCC. The IFNL3 rs12979860 CT and TT genotypes correlated with high baseline levels of α-fetoprotein (AFP; ≥20 ng/mL), advanced stage of fibrosis, diabetes, or lack of an SVR (all P < .05). Based on multivariate Cox regression analysis, age 60 years and older, low platelet count (<15 × 10 9 cells/L), AFP level of 20 ng/mL or greater, advanced stage fibrosis, diabetes, lack of an SVR, and the IFNL3 rs12979860 CT and TT genotypes were significant risk factors for HCC ( P < .05). Age 60 years and older, low numbers of platelets or high AFP level, and advanced fibrosis were risk factors for HCC among patients with a SVR. The IFNL3 rs12979860 genotype did not have a significant effect on risk for HCC among patients with SVRs, although some of these patients (with the CT or TT genotype) did develop HCC. Among patients without SVRs, only fibrosis stage and the IFNL3 rs12979860 CT and TT genotypes (hazard ratio, 1.80; 95% confidence interval, 1.06–3.07; P = .030) were independent risk factors for HCC. Conclusions Based on a retrospective study of patients treated for HCV infection, the IFNL3 rs12979860 CT and TT polymorphisms are associated with a risk for HCC, especially in patients without a SVR. [ABSTRACT FROM AUTHOR]

Background & Aims: Dual chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is common in areas endemic for either virus. Combination therapy with ribavirin and pegylated interferon (peginterferon) is the standard of care for patients with HCV monoinfection. We investigated the effects of combination therapy in patients infected with both HBV and HCV (genotypes 1, 2, or 3). Methods: The study included 321 Taiwanese patients with active HCV infection; 161 also tested positive for hepatitis B surface antigen (HBsAg) and 160 were HBsAg-negative (controls). Patients with HCV genotype 1 infection received peginterferon alfa-2a (180 μg) weekly for 48 weeks and ribavirin (1000–1200 mg) daily. Patients with HCV genotypes 2 or 3 received peginterferon alfa-2a weekly for 24 weeks and ribavirin (800 mg) daily. At 24 weeks posttreatment, patient samples were examined for a sustained virologic response (SVR) against HCV (serum HCV levels decreased to <25 IU/mL). Results: In patients with HCV genotype 1 infection, the SVR was 72.2% in dually infected patients vs 77.3% in monoinfected patients after treatment. For patients with HCV genotype 2/3 infections, the SVR values were 82.8% and 84.0%, respectively, after treatment. Serum HBV DNA eventually appeared in 36.3% of 77 dual-infected patients with undetectable pretreatment levels of HBV DNA; this was not accompanied by significant hepatitis. Posttreatment HBsAg clearance was observed in 11.2% of 161 dual-infected patients. Conclusions: Combination therapy with peginterferon alfa-2a and ribavirin is equally effective in patients with HCV monoinfection and in those with dual chronic HCV/HBV infection. [Copyright &y& Elsevier]

Summary: Objective: Diagnosis of acute hepatitis C (AHC) relies on documented positive-seroconversion of antibody to hepatitis C virus (anti-HCV) that is infrequently encountered. To clarify the epidemiology and clinical course of AHC, we tried to find more AHC patients from a computerized laboratory database by using a supplemental criterion of rising anti-HCV titer. Methods: All the computerized laboratory databases of anti-HCV and alanine aminotransferase (ALT) were reviewed. Candidates for AHC were identified by either anti-HCV positive seroconversion, rise of anti-HCV titer (signal to cut-off ratio (S/CO) ratio <40 to ≥40), or spontaneous HCV RNA clearance. AHC cases and their matched chronic hepatitis C controls were interviewed by a case–control study concerning risk factors. Results: AHC was identified in 123 patients (68 men and 55 women; median age: 48.4±13.9years), who had higher rates of recent surgery (p =0.037) and frequent injection therapy (p =0.036) compared to controls. Self-limited AHC was observed in 18 (19.1%, 95% confidence interval: 12.3–25.9%) of 94 AHC patients who had been followed for 6months, with a higher bilirubin level (≥2 vs. <2, p =0.007) compared to those evolved to chronic infection. Conclusions: Screening of a laboratory database for anti-HCV and ALT might uncover more AHC candidates to disclose the epidemiology and clinical course of AHC. [Copyright &y& Elsevier]

Background & Aims: This longitudinal study investigated the interactions and roles of hepatitis B virus (HBV) genotypes, pre-S deletions, and core promoter and precore mutations on the progression of liver disease in hepatitis B e antigen (HBeAg)-negative patients. Methods: A total of 141 HBeAg-negative patients without liver cirrhosis or hepatocellular carcinoma at study entry were recruited for this study, including 45 inactive HBV carriers and 96 patients with HBeAg-negative chronic hepatitis B. The HBV genotypes and the sequences of pre-S, core promoter, and precore regions were determined. Results: Compared with patients without developing liver cirrhosis, patients with the development of liver cirrhosis had higher rates of genotype C; pre-S deletions; C or G1753, T1762/A1764, T1766, and/or A1768 mutants; and G1799 variant. Cox regression analysis showed that older age, higher total bilirubin and HBV DNA levels, pre-S deletions, and T1766 and/or A1768 mutants were significantly associated with the development of liver cirrhosis. HBV with a complex mutation pattern (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutants) rather than a single mutation was associated with the development of liver cirrhosis, and the patterns of mutation combinations differed between HBV genotype B and C. Moreover, pre-S deletion was a significant risk factor for hepatocellular carcinoma. Conclusions: This study indicated that pre-S deletion and combined mutations of HBV are useful molecular markers for predicting the clinical outcomes of HBeAg-negative patients. [Copyright &y& Elsevier]

Background & Aims The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. Methods We collected data from 2 Taiwan HCC registry systems on 1509 patients (6–26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6–26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10 5 person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. Results Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10 5 person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6–9 years old, 10–14 years old, 15–19 years old, and 20–26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17–0.40), 0.34 (95% CI, 0.25–0.48), 0.37 (95% CI, 0.25–0.51), and 0.42 (95% CI, 0.32–0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992–2005 vs 1986–1992; P < .001 and 1986–1992 vs 1984–1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. Conclusions Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer. [ABSTRACT FROM AUTHOR]

Background & Aims We investigated the rate of relapse of hepatitis B virus (HBV) infection after entecavir therapy for chronic hepatitis B and the association between level of hepatitis B surface antigen (HBsAg) and relapse. Methods In a retrospective study, we analyzed data from 252 patients with chronic HBV infection who were treated with entecavir and met the Asian Pacific Association for the Study of the Liver treatment stopping rules (mean time, 164 ± 45 weeks) from January 2007 through June 2011 in Taiwan. Eighty-three were hepatitis B e antigen (HBeAg)-positive, and 169 were HBeAg-negative. Patients had regular post-treatment follow-up examinations for at least 12 months. Virologic relapse was defined on the basis of serum HBV DNA >2000 IU/mL after entecavir therapy. Clinical relapse was defined as a level of alanine aminotransferase >2-fold the upper limit of normal and HBV DNA >2000 IU/mL. Results Two years after therapy ended, 42% of HBeAg-positive patients had a virologic relapse, and 37.6% had a clinical relapse; 3 years after therapy ended, these rates were 64.3% and 51.6% for HBeAg-negative patients, respectively. On the basis of Cox regression analysis, factors independently associated with virologic and clinical relapse included old age, HBV genotype C, and higher baseline levels of HBsAg for HBeAg-positive patients and old age and higher end-of-treatment levels of HBsAg for HBeAg-negative patients. In HBeAg-positive patients, risk of HBV relapse increased with age ≥40 years and HBsAg level ≥1000 IU/mL at baseline ( P < .001). In HBeAg-negative patients, the combination of age (<55 years) and HBsAg level (<150 IU/mL) at the end of treatment was associated with a lower rate of virologic relapse (4.5% of HBeAg-negative patients had viral relapse at year 3). The decrease in level of HBsAg from month 12 of treatment until the end of treatment was greater in patients who did lose HBsAg after entecavir therapy compared with those who did not. Conclusions The combination of age and level of HBsAg is associated with relapse of HBV infection after treatment with entecavir. HBsAg levels might be used to guide the timing of cessation of entecavir treatment in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background & Aims: A phase 3 active-controlled study was conducted to assess the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of recombinant human albumin and interferon alfa-2b, in patients with chronic hepatitis C virus (HCV) genotype 2/3. Methods: In all, 933 patients were randomized to open-label subcutaneous treatment with pegylated interferon-alfa-2a (Peg-IFNalfa-2a) 180 μg/wk, or albIFN 900 or 1200 μg every 2 weeks for 24 weeks, each administered with oral ribavirin 800 mg/day. The primary end point of the study was sustained virologic response (SVR) (HCV-RNA level, <15 IU/mL at week 48). During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg, impacting 38% of this treatment arm. Results: By intention-to-treat analysis, SVR rates were 84.8% (95% confidence interval, 80.4%–88.6%), 79.8% (95% confidence interval, 74.9%–84.1%), and 80.0% (95% confidence interval, 75.1%–84.3%) with Peg-IFNalfa-2a, and albIFN 900 and 1200 μg, respectively. The primary hypothesis of noninferiority of SVR was established for albIFN 900 μg (P = .009) and 1200 μg (P = .006). Independent positive predictors of SVR by multivariate regression analysis were pretreatment HCV-RNA level less than 400,000 IU/mL, age younger than 45 years, body mass index less than 30 kg/m2, genotype 2, normal γ-glutamyl transpeptidase and increased alanine aminotransferase levels at baseline, fibrosis stage F0–F2, no steatosis, and Asian geographic region (Peg-IFNalfa-2a only). The 3 treatment groups showed similar rates of serious (7%–8%) and severe (13%–16%) adverse events, and discontinuations owing to adverse events (3.6%–5.5%). Conclusion: Albinterferon alfa-2b 900 μg every 2 weeks provides an alternative efficacious treatment option in patients with chronic HCV genotype 2 or 3. [Copyright &y& Elsevier]

Objective/aim: Hepatocellular carcinoma (HCC) surveillance is a common practice for patients with liver cirrhosis. The aims of the study were to assess impacts of surveillance and therapeutic options on survival of patients with HCC. Methods: A total of 1436 cirrhotic patients with newly diagnosed HCC were enrolled between January 2002 and December 2004. Patients with HCC detected within periodic surveillance were the surveillance group (n =318, 22.1%). The other patients with HCC incidentally detected were the non-surveillance group (n =1118, 77.95%). Initial treatment options were recorded and overall survival was analysed. Results: Compared with patients in the non-surveillance group, larger proportions of patients in the surveillance group possessed small tumours, at an early stage without vascular invasion or metastases, and afforded more curative treatment options including surgical resection, radiofrequency ablation and percutaneous ethanol injection. The overall survival was better for patients in surveillance (3-year survival rate: 59.1% versus 29.3%, p <0.001), early stages by Barcelona Clinic Liver Cancer (BCLC) staging or curative treatment options. Multivariate analysis demonstrated surveillance, hepatitis aetiology, alpha-fetoprotein, tumour gross type, tumour stage and treatment options were associated factors for patients’ survival. Moreover, surveillance patients in curative BCLC stage following the treatment guideline for HCC proposed by the American association for the study of liver disease (AASLD) had a significantly better 3-year survival rate (77.1% versus 55.2%, p <0.001). Conclusions: HCC surveillance for cirrhotic patients could detect HCC at early and curative stages. However, appropriate treatment options following AASLD guideline further improve the survival for patients in early stage. [Copyright &y& Elsevier]

Abstract: Aims: To assess the differences of long-term efficacy between plasma-derived and recombinant hepatitis B virus (HBV) vaccines and the effectiveness of catch-up vaccination in adolescents with undetectable anti-HBs. Methods: Before 1992, infants born in Taiwan were immunized using plasma-derived HB vaccine, and thereafter, by using recombinant HB vaccine. From the only junior middle school of a rural township in central–southern Taiwan, 1788 (93.7%) students from five cross-sectional screenings, grouping into three birth cohorts (Group I: born during 1984–1986, II: 1986–1992 and III: 1992–1995), were enrolled for checking HBsAg, anti-HBs and anti-HBc. Students with undetectable HBsAg and anti-HBs underwent a booster dose (2.5ug) of recombinant HB vaccine (Engerix-B; GlaxoSmithKline, Rixensart, Belgium) and had anti-HBs re-checked 3 weeks later. Individuals who had remained undetectable for anti-HBs completed the other two doses of HB vaccines at 1 and 6 months later. Results: The prevalence of HBsAg (11.4, 5.4 and 1.2%), anti-HBs (64.5, 44.1 and 36.0%) and anti-HBc (29.5, 12.5 and 4.4%) decreased from Group I to III (P <0.001 for trends). After a booster dose, the positive rates of anti-HBs increased up to 80.5% (16% increase) in Group I, 81.0% (36.9% increase) in Group II, and 94.4% (58.4% increase) in Group III. The percentages of anamnestic response increased with a trend (P <0.001). A total of 110 non-responders completed 3 doses of catch-up HB vaccination, but 3 cases (2.7%) of Group II, evoked primary vaccination response. Conclusion: Recombinant vaccine showed predominant disappearance rate (62.7%) of anti-HBs 12–15 years after vaccination, but provided better anamnestic response after a booster dose. It also showed high success rate (97.3%) in catch-up vaccination in adolescents. [Copyright &y& Elsevier]

Abstract: The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification and treatment allocation for hepatocellular carcinoma (HCC). We conducted this retrospective study to assess the efficacy of different treatment options for patients with initial HCC diagnosis. Survival rate and median survival times associated with different treatment options in each stage of BCLC classification were compared using the Kaplan–Meier method and log-rank test. A total of 3892 patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at 5 years. The median survival times decreased from 57.7 months in very early stage to 1.6 months in terminal stage. Surgical resection offered the best survival benefit for patients in very early, early and even intermediate stages. Transarterial embolisation and conformal radiotherapy offered survival benefits for selected patients in advanced and terminal stages. In conclusion, following the treatment schedules allocated by BCLC staging had survival benefits for HCC patients. [Copyright &y& Elsevier]

Objective: In Taiwan, the carrier rate of hepatitis B surface antigen is 15% to 20%, one of the highest in the world. Among chronic hepatitis B (CHB) patients, hepatitis B e antigen (HBeAg)-negative accounts for approximately 40% to 50% of these patients. A recent study found that peginterferon alfa-2a (40 KD) is more effective than lamivudine in treating HBeAg-negative CHB, but its cost-effectiveness has not been evaluated. Our objective is to evaluate the incremental cost-effectiveness of 48 weeks of peginterferon alfa-2a compared to 48 weeks of lamivudine, from the perspective of the Taiwan Bureau of National Health Insurance. Methods: A Markov model was used to simulate the natural history of HBeAg-negative CHB in a cohort of 40-year-old patients. Efficacy, disease progression, economic, and quality-of-life data were derived from published literature and a survey of clinical experts in Taiwan. Life expectancy, quality-adjusted life expectancy, lifetime costs in New Taiwan Dollars (NTD) (1 USD = 31.96 NTD), and incremental cost-effectiveness ratios (ICERs) were calculated. Results: The gain in quality-adjusted life-years (QALYs) for 48 weeks of peginterferon alfa-2a compared to 48 weeks of lamivudine was 0.45 at an additional cost of 157,000 NTD (4900 USD), resulting in an ICER of 347,000 NTD (10,900 USD) per QALY gained. The 95% central range for the ICER from a probabilistic sensitivity analysis was 228,000–566,000 NTD (7100–17,700 USD). Conclusions: In HBeAg-negative CHB, 48 weeks of treatment with peginterferon alfa-2a compared to 48 weeks of lamivudine appears to offer life expectancy and quality-of-life improvements at an acceptable cost-effectiveness ratio. [ABSTRACT FROM AUTHOR]

Background: To determine the utility of contrast-enhanced ultrasonography (CEUS) in assessing hepatic tumors with central feeding arteries found by color/power Doppler ultrasonograophy (CDUS/PDUS). Methods: We prospectively studied 37 hepatic tumors (34 patients), with a mean size of 2.9cm and each having a central feeding artery, by CDUS/PDUS. The CEUS was performed with a galactose-based microbubble contrast agent. The detection of a spoke-wheel sign was interpreted as evidence of focal nodular hyperplasia (FNH). All patients underwent tumor biopsies or surgical resection. Results: CEUS showed a central feeding artery with a spoke-wheel sign in 36 tumors, including 34 FNHs and 2 hepatocellular carcinomas. The remaining tumor was demonstrated to be FNH despite the absence of a spoke-wheel sign as detected by CEUS. The sensitivity of the spoke-wheel sign or central scar for FNH was 97.1% (34/35), 40% (14/35), 28.6% (10/35), 50% (8/16) and 0% (0/15) for CEUS, CDUS/PDUS, dynamic computed tomography (CT) or magnetic resonance imaging (MRI), hepatic angiography and liver scintigraphy, respectively. The two hepatocellular carcinomas showed scirrhous changes histologically. Conclusions: CEUS is more sensitive than CDUS/PDUS, dynamic CT, MRI, hepatic angiography and liver scintigraphy in the detection of the spoke-wheel sign or central scar in FNH. Scirrhous hepatocellular carcinoma should be included in the differential diagnosis for liver tumors with spoke-wheel sign detected by CEUS. [ABSTRACT FROM AUTHOR]

Abstract: In Taiwan, decrease of both infection and carrier rates of hepatitis B virus (HBV) have been documented especially in metropolitan areas after universal HBV vaccination. This study investigated HBV infection status in a rural township 15 years after the program began. Three cross-sectional studies were conducted in 1999, 2000 and 2003, to recruit all the students of the only junior middle school, born from July 1984 to June 1991, in a township in central Taiwan. Serum samples were tested for HBsAg, anti-HBs and anti-HBc. Subjects identified to be neither positive for HBsAg nor anti-HBs were given a booster dose of HBV vaccine. Subjects lacking an anamnestic anti-HBs response were given a complete 3-dose vaccination. A total of 1454 (98.5%) students responded. The prevalence rate of HBsAg decreased 57% [from 12.5% in 1984 to 5.4% in 1991, P <0.005 (χ 2-test for linear trends)], and anti-HBc positive rate dropped 68% (from 31.9 to 10.2%, P <0.001). An anamnestic anti-HBs response developed after a vaccine booster among 433 (72%) anti-HBs negative and 12 (66.7%) anti-HBc alone subjects. And 93 (94.9%) anti-HBs negative and 1 (16.7%) anti-HBc alone subject developed a primary anti-HBs response after catch-up vaccination. Viremia was detected for two anti-HBc alone subjects without anamnestic or primary response. The vaccination program has decreased the number of those infected and carrier rates in either urban or rural areas in Taiwan. However, the prevalence of HBsAg and anti-HBc in rural area were much higher than urban area. [Copyright &y& Elsevier]